Patients with spinal cord or brachial plexus injury often develop chronic pain which is generally persistent and resistant to conventional pain treatments. Experimental and clinical observations suggest that abnormal central nociceptive systems contribute to such sustained neuropathic pain in chronic pain patients. We hypothesize that functional reorganization, or plasticity, of the central nociceptive system may play an important role in mechanisms of chronic pain in patients with spinal cord or brachial plexus injury. Such changes may result in altered pharmacologic responses to conventional analgesics and other pain treatments. Three experiments using positron emission tomography (PET) and neuronal activation techniques are proposed to investigate functional reorganization of the central nociceptive system and its responses to pharmacologic interventions. The PET activation method gives us opportunities to examine dynamically-modulated central nociceptive system in living humans under physiological conditions. The method can determine three-dimensional distributions of the central nociceptive activity in non-invasive and repetitive manners. To test the integrity of the central nociceptive system, quantitatively controlled laser stimuli will be used. The laser stimulation enables us to correlate between PET, psychophysical, and neurophysiological measures. By using these techniques, we will examine, first, normal patterns of the central nociceptive activity and effects of antidepressants on these systems. Second, using a longitudinal experimental design, we will determine the occurrence of cerebral functional reorganization in patients who have developed chronic pain. Third, using a cross-sectional experimental design, we will investigate patterns of cerebral functional reorganization in patients with different degrees of chronic pain and effectiveness of antidepressants. The proposed research will reveal neurophysiological insights into chronic pain and the effects of pharmacologic interventions at the cerebral level, which may help in the development of new strategies to manage and treat chronic pain patients with spinal cord or brachial plexus injury. Understanding functional reorganization in the central nociceptive system may enable preventive interventions for chronic pain. The PET method established in this research will be applicable for examining other forms of therapeutic interventions in future chronic pain research.